Screening Tool Could Predict Risk of Developing AML Years Before Disease Onset

The incidence of acute myeloid leukemia (AML) increases as people age, but the disease can often appear suddenly in patients, without any detectable early symptoms. However, new research has identified the origins of AML, which can be detectable more than 5 years before the disease develops.

The results, published in Nature, found that blood tests can reveal the roots of AML in healthy patients by looking for changes in DNA code.

“We have been able to identify people in the general population who have traces of mutations in their blood that represent the first steps in how normal blood cells begin on a pathway of becoming increasingly abnormal and puts them at risk of progressing to AML,” co-principal investigator John Dick, PhD, FRS, senior scientist at Princess Margaret Cancer Centre, University Health Network, said in a statement. “We can find these traces up to 10 years before AML actually develops. This long-time window gives us the first opportunity to think about how to prevent AML.”

The researchers used data from a large European population health and lifestyle study that tracked 550,000 people over 20 years. The team used data from more than 100 participants who developed AML 6 to 10 years after joining the study, plus data from an age-matched cohort of more than 400 people who did not develop AML.

They found that years before an individual was diagnosed with AML, the blood system started to pick up mutations, which allowed the team to predict who had been at risk of disease progression.

The challenge is that recurrent AML mutations also accumulate in healthy individuals who do not develop AML. The researchers were able to use deep sequencing to analyze genes to distinguish between individuals who have a high risk of developing AML and those with benign age-related clonal hematopoiesis, which is when blood stem cells acquire mutations and become a little more proliferative.

“Our study provides, for the first time, evidence that we can identify people at risk of developing AML many years before they actually develop this life-threatening disease,” said George S. Vassiliou, FRCPath, MRCP, PhD, who is one of the joint leaders of the project and a consultant hematologist at Cambridge University Hospitals. “We hope to build on these findings to develop robust screening tests for identifying those at risk and drive research into how to prevent or stall progression towards AML. Our aspiration is that one day, AML prevention would provide a compelling alternative to treatment.”

Reference

Abelson S, Gollord G, Ng SWK, et al. Prediction of acute myeloid leukaemia risk in healthy individuals [published online June 9, 2018]. Nature. doi: 10.1038/s41586-018-0317-6.